Potassium channels (KCh) belong to a class of transmembrane proteins with more than 100 genes coding for the principle subunits. KCh are involved in many physiological functions, such as cell proliferation, growth, apoptosis, reactive oxygen species creation, inflammasome formation, and insulin secretion. By opening or blocking KCh and thus adjusting the potassium-ion concentration in cellular organelles, a cell can control cell-membrane potential, contribute to cardiac action potentials and neurotransmitter release, and affect various critical biological functions. It has been recently determined that KCh is a potential pharmacological target in treating cancer, autoimmune disease, neuroprotection, cardioprotection, and diabetes.
Typical research tools for KCh study include a patch-clamp technique, a fluxOR™ assay method using Tl+ ion and corresponding fluorescent probes, and a Rb+ ion method. While these methods have been demonstrated to be useful for high-throughput screening of drugs with a certain type of potassium channels, related art is limited in understanding of the relationship(s) in a multi-factor pathway in the cell. Due to the lack of fluorescent potassium sensors targeting mitochondria, most research on mitochondrial KCh uses indirect experimental methods, leaving lots of uncertainty in the research conclusion.
Recent research demonstrated that K+ flux through the inner mitochondrial membrane had a significant effect in insulin secretion, inflammasome formation, and cell apoptosis. Development of a mitochondria-targeting K+ sensor is critical in investigation of the potassium-related mitochondrial signaling processes and the pathway of the disease, including single cell metabolic analysis, cancer studies, and new drug screening.